Rare craniofacial clefts: Tessier no. 4 clefts

A major difficulty in understanding rare craniofacial clefts arises from the fact that previous reports have focused on a single case or have grouped together different types of rare clefts. Less than 50 Tessier no. 4 clefts have been reported. This paper examines our experience with eight patients treated primarily or secondarily for Tessier no. 4 clefts. A treatment plan is recommended. The primary early concern is protection of the eye. Early correction of soft-tissue deformities should include skin, muscle, and lining of the orbit, cheek, and oral cavity. Contrary to the dictum that all soft tissue must be preserved, the medial portion of the upper lip from the cleft to the philtral ridge must be resected to prevent poorly camouflaged scars, muscle deficiency, and macrostomia. Bone grafting should be undertaken at an early age using calvarial bone. Late operations will be necessary for correction of medial and lateral canthal position, epiphora, lower eyelid skin deficiency, and further bony augmentation.     

Common craniofacial anomalies: facial clefts and encephaloceles

The wide variety of craniofacial malformations makes classification difficult. A simple classification system allows an overview of the current understanding of the causes, assessments, and treatments of the most frequently encountered craniofacial anomalies. Facial clefts and encephaloceles are reviewed with respect to their diverse causes, pathogenesis, anatomical features, and treatments. Approaches to the surgical treatment of these conditions are reviewed.     

Tissue expansion in the reconstruction of Tessier craniofacial clefts: a series of 17 patients

Tessier craniofacial clefts are among the most surgically challenging examples of craniofacial dysmorphology. These clefts are characterized by hypoplasia of soft-tissue and skeletal elements throughout the three-dimensional extent of the cleft. Whereas bone grafting and craniofacial osteotomies have been successful toward correcting the underlying skeletal abnormalities, the ultimate success of these reconstructions has been limited by the deficiency of skin and soft tissue. This deficiency demands reconstruction ideally with tissue of like texture, consistency, and, especially in the face, color. Craniofacial tissue expansion was used toward reconstructing these facial clefts with like-quality tissue, allowing for tension-free reconstruction after osteotomy and bone grafting. Seventeen patients with Tessier craniofacial clefts underwent preoperative craniofacial soft-tissue expansion in the surgical management of their clefts. Tissue expansion was used in the primary correction of facial clefts in eight patients, with nine patients undergoing expansion before secondary surgery. In this series, tissue expansion has evolved as an important element in overcoming the skin and soft-tissue deficiency associated with these clefts, allowing for tension-free closure and improved aesthetic results in these surgically challenging patients.     

New biomaterials and methods for craniofacial bone defect: chondroid bone grafts in maxillary alveolar clefts

The purpose of this study was to evaluate autogenous osteogenic marrow within chondroid bone grafts in simulated alveolar defects of mice in order to determine the ability of the graft material to effectively close the cleft from an osseous standpoint and to observe the effect of the grafting procedure. Critical-sized defects were made in the premaxillary bones of male mice using a surgical trephine and a low-speed dental engine as a model of the maxillary alveolar cleft for testing bone-inductive agents. Premaxillary trephine defects were not repaired by fibrous tissue or bone formation 30 days after operation. This nonhealing bony wound of the premaxilla in mice may be useful as a model for studying the effect of bone-inductive agents on the healing of alveolar clefts. Distraction osteogenesis is a recently advanced principle of bone lengthening in which a long bone separated by osteotomy is subjected to slow progressive distraction using an external fixation device. The osteotomy site was surrounded by an external callus consisting of hyaline cartilage. The callus contained a lot of chondroid bone. The transplant bone within chondroid bone was characterized by bone formation and remodeling 30 days after transplantation. Throughout the experiment, our findings demonstrated, for the first time, that the transplant bone that contains chondroid bone may be used clinically in relation to craniofacial bone defects to improve the treatment of bone grafts.     

Electroporation of craniofacial mesenchyme

Electroporation is an efficient method of delivering DNA and other charged macromolecules into tissues at precise time points and in precise locations. For example, electroporation has been used with great success to study neural and retinal development in Xenopus, chicken and mouse ^1-10. However, it is important to note that in all of these studies, investigators were not targeting soft tissues. Because we are interested in craniofacial development, we adapted a method to target facial mesenchyme.When we searched the literature, we found, to our surprise, very few reports of successful gene transfer into cartilaginous tissue. The majority of these studies were gene therapy studies, such as siRNA or protein delivery into chondrogenic cell lines, or, animal models of arthritis ^11-13. In other systems, such as chicken or mouse, electroporation of facial mesenchyme has been challenging (personal communications, Dept of Craniofacial Development, KCL). We hypothesized that electroporation into procartilaginous and cartilaginous tissues in Xenopus might work better. In our studies, we show that gene transfer into the facial cartilages occurs efficiently at early stages (28), when the facial primordium is still comprised of soft tissue prior to cartilage differentiation.Xenopus is a very accessible vertebrate system for analysis of craniofacial development. Craniofacial structures are more readily visible in Xenopus than in any other vertebrate model, primarily because Xenopus embryos are fertilized externally, allowing analyses of the earliest stages, and facilitating live imaging at single cell resolution, as well as reuse of the mothers ¹⁴. Among vertebrate models developing externally, Xenopus is more useful for craniofacial analysis than zebrafish, as Xenopus larvae are larger and easier to dissect, and the developing facial region is more accessible to imaging than the equivalent region in fish. In addition, Xenopus is evolutionarily closer to humans than zebrafish (˜100 million years closer) ¹⁵. Finally, at these stages, Xenopus tadpoles are transparent, and concurrent expression of fluorescent proteins or molecules will allow easy visualization of the developing cartilages. We anticipate that this approach will allow us to rapidly and efficiently test candidate molecules in an in vivo model system.     

Common craniofacial anomalies: conditions of craniofacial atrophy/hypoplasia and neoplasia

The spectrum of craniofacial malformations includes conditions of congenital and acquired etiology. The conditions of craniofacial atrophy and hypoplasia may arise primarily or secondary to previous therapeutic interventions. The conditions of progressive hemifacial atrophy (Romberg disease) and radiation-induced hypoplasia will be reviewed on the basis of their etiology, pathogenesis, anatomy, and treatment. Approaches to the surgical management of these conditions will be discussed. The craniofacial neoplastic conditions of fibrous dysplasia, neurofibromatosis, and craniofacial tumors will also be reviewed and discussed.     

Preservation of protein clefts in comparative models

Background  

Comparative, or homology, modelling of protein structures is the most widely used prediction method when the target protein has homologues of known structure. Given that the quality of a model may vary greatly, several studies have been devoted to identifying the factors that influence modelling results. These studies usually consider the protein as a whole, and only a few provide a separate discussion of the behaviour of biologically relevant features of the protein. Given the value of the latter for many applications, here we extended previous work by analysing the preservation of native protein clefts in homology models. We chose to examine clefts because of their role in protein function/structure, as they are usually the locus of protein-protein interactions, host the enzymes' active site, or, in the case of protein domains, can also be the locus of domain-domain interactions that lead to the structure of the whole protein.     

Orofacial clefts and infections during pregnancy

Orofacial clefts (OFCs) are common congenital malformations of the lip, palate, or both caused by complex genetic and environmental factors. Specific antibodies against viruses influenza, rubella, cytomegalovirus, Epstein-Barr, parotitis and hepatitis B were investigated serologically in children with orofacial clefts and in their mothers. The results were compared with those obtained in control children and their mothers. Evaluation of the results and their statistical processing supports the assumption that infection during pregnancy may have occurred in the series studied induced by viruses of influenza, rubella, cytomegalovirus and possibly also by the Epstein-Barr virus. No association with the viruses of hepatitis B and parotitis was established.     

Genesis of alcohol-induced craniofacial dysmorphism

The initial diagnosis of fetal alcohol syndrome (FAS) in the United States was made because of the facial features common to the first cohort of patients. This article reviews the development of an FAS mouse model whose craniofacial features are remarkably similar to those of affected humans. The model is based on short-term maternal treatment with a high dosage of ethanol at stages of pregnancy that are equivalent to Weeks 3 and 4 of human gestation. At these early stages of development, alcohol's insult to the developing face is concurrent with that to the brain, eyes, and inner ear. That facial and central nervous system defects consistent with FAS can be induced by more "realistic" alcohol dosages as illustrated with data from an oral alcohol intake mouse model in which maternal blood alcohol levels do not exceed 200 mg/dl. The ethanol-induced pathogenesis involves apoptosis that occurs within 12 hrs of alcohol exposure in selected cell populations of Day 7, 8, and 9 mouse embryos. Experimental evidence from other species also shows that apoptosis underlies ethanol-induced malformations. With knowledge of sensitive and resistant cell populations at specific developmental stages, studies designed to identify the basis for these differing cellular responses and, therefore, to determine the primary mechanisms of ethanol's teratogenesis are possible. For example, microarray comparisons of sensitive and resistant embryonic cell populations have been made, as have in situ studies of gene expression patterns in the populations of interest. Studies that illustrate agents that are effective in diminishing or exacerbating ethanol's teratogenesis have also been helpful in determining mechanisms. Among these agents are antioxidants, sonic hedgehog protein, retinoids, and the peptides SAL and NAP.